Approach to Stereotactic Body Radiotherapy for the Treatment of Advanced Hepatocellular Carcinoma in Patients with Child-Pugh B-7 Cirrhosis.

OPINION STATEMENT: Patients with hepatocellular carcinoma (HCC) with underlying Child-Pugh B-7 cirrhosis benefit from management from an experienced, multidisciplinary team. In patients with localized disease who meet criteria for liver transplant, establishing care at a liver transplant center is crucial. For those awaiting transplant, local bridge therapies have emerged as a strategy to maintain priority status and eligibility. Multiple liver-directed therapies exist to provide locoregional tumor control. The careful selection of locoregional therapy is a multidisciplinary endeavor that takes into account patient factors including tumor resectability, underlying liver function, performance status, previous treatment, tumor location/size, and vascular anatomy to determine the optimal management strategy. Technological advances in external beam radiation therapy have allowed stereotactic body radiation therapy (SBRT) to emerge in recent years as a versatile and highly effective bridge therapy consisting of typically between 3 and 5 high dose, highly focused, and non-invasive radiation treatments. When treating cirrhotic patients with HCC, preserving liver function is of utmost importance to prevent clinical decline and decompensation. SBRT has been shown to be both safe and effective in carefully selected patients with Child-Pugh B cirrhosis; however, care must be taken to prevent radiation-induced liver disease. This review summarizes the evolving role of SBRT in the treatment of HCC in patients with Child-Pugh B-7 cirrhosis.

Weight loss does not decrease risk of breast cancer-related arm lymphedema.

BACKGROUND: The goal of this study was to determine the relationship between postoperative weight change and breast cancer-related lymphedema (BCRL). METHODS: In this cohort study, 1161 women underwent unilateral breast surgery for breast cancer from 2005 to 2020 and were prospectively screened for BCRL. Arm volume measurements were obtained via an optoelectronic perometer preoperatively, postoperatively, and in the follow-up setting every 6 to 12 months. Mean follow-up from preoperative baseline was 49.1 months. The main outcome was BCRL, defined as a relative volume change of the ipsilateral arm of ≥10% at least 3 months after surgery. RESULTS: A total of 92 patients (7.9%) developed BCRL. Net weight loss versus net weight gain from baseline to last follow-up was not protective against developing BCRL (hazard ratio, 1.38; 95% confidence interval, 0.89-2.13; P = .152). CONCLUSIONS: Although weight loss may be recommended as part of an individualized lifestyle management program for overall health, weight loss alone may not decrease the risk of developing BCRL.

Integrating Symptoms Into the Diagnostic Criteria for Breast Cancer-Related Lymphedema: Applying Results From a Prospective Surveillance Program.

OBJECTIVE: The objectives of this study were to determine whether patients reporting symptoms are more likely to develop lymphedema and to describe the temporal relationship between symptom onset and lymphedema. METHODS: This was a prospective longitudinal cohort study of 647 women treated for breast cancer and screened for lymphedema using arm volume measurements and subjective questionnaires (n = 647; 2284 questionnaires [median 3.5 per patient, range = 1-24]). Primary study outcome was lymphedema (relative volume change ≥10%). The Kaplan-Meier method was used to estimate cumulative lymphedema incidence. Cox proportional hazards models were used to assess the relationship between symptoms, other risk factors, and lymphedema. RESULTS: A total of 64 patients (9.9%) developed lymphedema. On multivariable analysis, patients reporting increased arm size (hazard ratio = 3.09, 95% CI = 1.62-5.89) were more likely to progress to lymphedema than those who did not report this symptom. Of those who developed lymphedema, 37 (58%) reported an increased arm size a median of 6.1 months before lymphedema onset (range = 68.6 months before to 50.2 months after lymphedema onset). CONCLUSION: Patients at risk of lymphedema who report increased arm size might do so prior to lymphedema onset and are at 3 times the risk of lymphedema as patients not reporting this symptom. Even without objective or observable edema, these patients should be followed vigilantly and considered for early intervention. Symptoms should be incorporated into screening and diagnostic criteria for lymphedema. IMPACT: This study shows that patients at risk for breast cancer-related lymphedema who report increased arm size should be considered at high risk for progression to lymphedema-even without edema on measurement or clinical examination-and should be followed vigilantly, with consideration of early intervention. LAY SUMMARY: If you are at risk of lymphedema and you feel as though your arm size has increased, you might develop lymphedema, and you are at 3 times the risk of lymphedema as patients not reporting this symptom. Even without measurable or observable edema, you should be followed vigilantly and consider early intervention.

Patients who report cording after breast cancer surgery are at higher risk of lymphedema: Results from a large prospective screening cohort.

OBJECTIVES: To identify the association between cording and breast cancer-related lymphedema (BCRL); describe time course, location, symptoms and functional impairments. METHODS: A total of 1181 patients were prospectively screened for BCRL after breast cancer (BC) surgery, including patient-reported outcome measures (4193) and perometric arm volume measurements (BCRL defined as relative or weight-adjusted volume change [RVC or WAC] ≥10% ≥3 months postoperatively). RESULTS: A total of 374/1181 patients (31.7%) reported cording first a median of 4.5 months postoperatively, and were more likely to: have body mass index less than 30 kg/m2 ; be less than 55 years of age; have had mastectomy, axillary lymph node dissection, regional lymph node radiation, neoadjuvant chemotherapy (all P < .001), or RVC/WAC ≥10% (P = .002). Patients who reported cording had 2.4 times the odds of developing BCRL compared to those who did not (odds ratio = 2.40; 95% confidence interval = 1.40-4.11; P = .002), and most frequently reported these symptoms: tenderness (61.2%), aching (60.7%), and firmness/tightness (59.8%). On multivariable analysis, cording was significantly correlated with functional difficulty for 17 actions. CONCLUSIONS: Patients frequently present with cording, potentially months after BC surgery. Risk factors for and symptoms of cording are identified, and treatment is recommended. Patients reporting cording are at higher risk of BCRL, therefore, cording should be incorporated into BCRL risk stratification.

Incidence of peripheral edema in patients receiving PI3K/mTOR/CDK4/6 inhibitors for metastatic breast cancer.

PURPOSE: This study evaluated development of edema in patients receiving PI3K/mTOR/CDK4/6 targeted therapy for metastatic breast cancer (MBC). METHODS: We reviewed medical records of 160 patients receiving targeted therapy with PI3K/mTOR/CDK4/6 inhibitors to treat MBC (n = 160; 185 treatment occurrences). Clinicopathologic data, treatment details, and edema incidence were recorded. RESULTS: Edema incidence was 43.1% (69/160) overall and 25.6% (41/160) in the upper extremity ipsilateral to the treated breast. In 185 therapy regimens administered, 6.8% of patients on a PI3K inhibitor, 8.8% of patients on an mTOR inhibitor, and 9.2% of patients on a CDK4/6 inhibitor experienced new onset or worsened preexisting upper extremity edema. Further, 9.1% of patients on a PI3K inhibitor, 18.8% of patients on an mTOR inhibitor, and 10.5% of patients on a CDK4/6 inhibitor experienced new onset or worsened preexisting edema elsewhere in the body. Multivariate logistic regression showed that, beyond the established breast cancer-related lymphedema (BCRL) risk factors [axillary lymph node dissection (Odds Ratio (OR) 2.69, p = 0.020), regional lymph node irradiation (OR 6.47, p < 0.001), and body-mass index ≥ 30 kg/m2 (OR 3.46, p = 0.006)], a relative decrease in serum albumin after 3 months of treatment increased risk of developing edema (OR 2.07, p = 0.062). Neither duration nor type of therapy were significant risk factors for edema. CONCLUSION: PI3K/mTOR/CDK4/6 inhibitors may influence the development of edema, which may cause or exacerbate progression of BCRL in patients with MBC. The varied incidence of edema between therapeutic regimens warrants vigilant monitoring of patients treated with these therapies, especially those at high risk of developing BCRL.

Breast cancer-related lymphedema: risk factors, precautionary measures, and treatments.

Breast cancer-related lymphedema (BCRL) is a negative sequela of breast cancer treatment, and well-established risk factors include axillary lymph node dissection (ALND) and regional lymph node radiation (RLNR). BCRL affects approximately 1 in 5 patients treated for breast cancer, and it has a significant negative impact on patients' quality of life after breast cancer treatment, serving as a reminder of previous illness. This paper is a comprehensive review of the current evidence regarding BCRL risk factors, precautionary guidelines, prospective screening, early intervention, and surgical and non-surgical treatment techniques. Through establishing evidence-based BCRL risk factors, researchers and clinicians are better able to prevent, anticipate, and provide early intervention for BCRL. Clinicians can identify patients at high risk and utilize prospective screening programs, which incorporate objective measurements, patient reported outcome measures (PROM), and clinical examination, thereby creating opportunities for early intervention and, accordingly, improving BCRL prognosis. Innovative surgical techniques that minimize and/or prophylactically correct lymphatic disruption, such as axillary reverse mapping (ARM) and lymphatic-venous anastomoses (LVAs), are promising avenues for reducing BCRL incidence. Nonetheless, for those patients with BCRL who remain unresponsive to conservative methods like complete decongestive therapy (CDT), surgical treatment options aiming to reduce limb volume or restore lymphatic flow may prove to be palliative or corrective. It is only through a strong team-based approach that such a continuum of care can exist, and a multidisciplinary approach to BCRL screening, intervention, and research is therefore strongly encouraged.

Perometry versus simulated circumferential tape measurement for the detection of breast cancer-related lymphedema.

PURPOSE: Despite increasing emphasis on screening and early intervention for breast cancer-related lymphedema (BCRL), there is marked heterogeneity in diagnostic methodology, including for volumetric measures. This retrospective study compared two volumetric modalities, perometry and simulated circumferential tape measurement (anatomic- and interval-based), for BCRL detection. METHODS: Between 2005 and 2017, 287 female patients with unilateral breast cancer were prospectively screened for BCRL by perometry and the relative volume change (RVC) formula. Circumferential measurement was performed by sampling at five anatomic landmark-based points or 4-cm intervals from pairs of perometer arm diameter measurements. Volumetric conversion was by a frustum model. The Bland-Altman method was used to compare segmental volume differences. Confusion matrix analysis was performed for each circumferential measurement technique against perometry. RESULTS: Median follow-up was 34.7 months over 4 postoperative visits. There was no difference in total arm volume comparing any of the circumferential measurement techniques to perometry. Landmark-based methods significantly underestimated upper arm volume (mean difference - 207 mL [- 336, - 78 mL]) and overestimated forearm volume (mean difference + 170 mL [+ 105, + 237 mL]). Landmark-based methods had greater sensitivity and specificity compared to 4-cm interval methods for detection of both RVC ≥ 10 and 5-10%. Landmark-based methods were comparable to perometry for detection of RVC ≥ 10%, but sensitivity was only 63.2-66.7% for RVC 5-10%. CONCLUSIONS: This hypothesis-generating study suggested the superiority of anatomic landmark-based circumferential tape measurement compared to interval-based methods, while generating questions about the underestimation of upper arm volume and overestimation of forearm volume of circumferential tape measurement compared to perometry.